The objectives of the research proposal are (1) to study the enzymatic nature of the microsomal oxidizing activity and (2) to determine the effect of ethanol ingestion on hepatic collagen metabolism. In the study of the enzymatic nature of the microsomal ethanol oxidizing activity, components of the microsomal mixed function oxidase system (principally: cytochrome P-450, NADPH-cytochrome c reductase, and lipid) will be separated from each other and from contaminating catalase and alcohol dehydrogenase. To be determined are the ability of one or of a combination of these components to catalyze the oxidation of ethanol, the mechanism of oxidation, and the inducibiliy of the individual components by feeding ethanol. The effect of ethanol on hepatic collagen metabolism will be studied in animals and humans. Studied in animals will be the effect of ethanol ingestion on (a) collagen synthesis, as measured by the hepatic pool of free proline, the incorporation of proline into collagen, and the activity of protocollagen proline hydroxylase; (b) collagen degradation, as measured by the urinary excretion of peptide hydroxyproline and liver histology. In alcoholic patients serial determinations of hepatic protocollagen proline hydroxylase and urinary excretion of peptide hydroxyproline will be correlated with liver histology to determine (a) if these parameters are of predictive value in the subsequent development of fibrosis and cirrhosis and (b) the effect of prednisolone therapy on the development of fibrosis in alcoholic hepatitis.